warfarin and Swine-Diseases

Selenium may be related to the hepatic metabolism of the coumarin compounds aflatoxin B1 and warfarin. Selenium evidently increased the pharmacologic activity of warfarin, probably due to a displacement of warfarin from albumin by selenium, the close relationship among selenium, vitamin E, and sulphur-containing groups (eg, glutathione), or the antioxidant effect of selenium. A diet containing selenium in a concentration of 2.5 mg/kg of feed was protective against the toxic effects of both coumarins in pigs given 4 daily oral doses of 0.2 mg/kg of body weight. Selenium, as glutathione peroxidase, at least in part, protects the hepatic cells against the toxic effects of aflatoxin B1 and warfarin. The protection was demonstrated by alteration of clinical responses and hematologic (prothrombin times), electrophoretic, and clinical chemistry values. It also was demonstrated that selenium at 2.5 mg/kg of feed does not produce toxic effects; however, dietary selenium at a concentration of 5 mg/kg (and in the presence of both toxic agents) was toxic for young pigs within the 3-week experimental period. Warfarin was more active as an anticoagulant than aflatoxin B1.

Topics: Aflatoxin B1; Aflatoxins; Animals; Biotransformation; Blood Proteins; Body Weight; Diet; Drug Interactions; Liver; Male; Prothrombin Time; Selenious Acid; Selenium; Swine; Swine Diseases; Warfarin

Observations on the interactions of cadmium (Cd) x aflatoxin B1 (AFB1) and Cd x warfarin included several variables of animal performance and hematology. Cadmium was fed daily for 40 days (groups IV, V, VI) and a Cd-free diet was fed to groups I, II, and III. Groups II and V were treated with AFB1, and groups III and VI were treated with warfarin--each for 5 days during the 5th week of the experiment and the effects were observed for 10 days. All pigs fed the diet with added Cd had developed severe anemia by the 4th week of the experiment. The incorporation of this toxic concentration of Cd (83 micrograms/g) in the diet seemed to have blocked the liver microsomal enzyme system (cytochrome P-450), diminishing the toxic effects of 5 daily oral doses (0.2 mg/kg of body wt) of AFB1 (group V pigs), but enhancing synergistically the toxic anticoagulant effects of the same doses of warfarin in young pigs (group VI). The data presented also indicated that the feeding of toxic concentrations of Cd stimulated increased glutathione peroxidase activity, which conjugated the AFB1 epoxides with their excretion as reduced glutathione but enhanced the toxic anticoagulant effects of warfarin in young pigs.

Topics: Aflatoxin B1; Aflatoxins; Anemia, Hypochromic; Animal Feed; Animals; Cadmium; Carcinogens; Drug Synergism; Leukocyte Count; Male; Swine; Swine Diseases; Warfarin

The purpose of this experiment was to compare the toxic effects of aflatoxin B1 (AFB1) and warfarin in pigs and to determine whether these have an additive effect in these pigs fed dietary Cd. Cadmium was provided daily through the diets of 2 concentrations (0 or control, and 83 micrograms/g of diet) during the 40 days of the experiment. At the start of the 5th week, AFB1 and warfarin were given in 5 daily doses (each dose 0.2 mg/kg of body weight) and the effects were determined for 10 days (starting with the 1st treatment day). Aflatoxin B1 given to the pigs fed the control diet (0 Cd) was toxic, inducing significantly increased alkaline phosphatase, sorbitol dehydrogenase, and aspartate aminotransferase activities and the prothrombin time (PT) and activated partial thromboplastin time (APTT) and significantly decreased values in serum total protein, alpha-globulin, beta-globulin, gamma-globulin, and fibrinogen. There was no effect on blood urea nitrogen. The treatment with warfarin was more effective in producing earlier and significantly longer PT and APTT. In the pigs fed the diet with the added Cd, differences in activity of alkaline phosphatase, sorbitol dehydrogenase, aspartate aminotransferase values, but not blood urea nitrogen, as well as differences in intensity and duration of response in PT and APTT occurred when pigs were dosed daily for 5 days after AFB1 or warfarin. It is concluded that dietary Cd (83 micrograms/g of diet) in young pigs has an inhibitory effect on AFB1 toxicity and an enhancing synergistic effect with warfarin.

Topics: Aflatoxin B1; Aflatoxins; Animal Feed; Animals; Blood Proteins; Blood Urea Nitrogen; Cadmium; Cadmium Poisoning; Carcinogens; Chemical and Drug Induced Liver Injury; Liver Diseases; Male; Swine; Swine Diseases; Warfarin

The effects of feeding dietary cadmium (83 micrograms/g of diet) to young pigs on the distributions of copper, iron, and zinc in urine samples and in kidney, liver, and muscle tissues was determined. The diet with added Cd resulted in renal and hepatic tissue concentrations of 42.90 +/- 10.57 micrograms/g and 7.90 +/- 2.37 micrograms/g, respectively, at the 40th day of the experiment. Iron was found to decrease at the same time, which predisposed to the anemic condition of these pigs. The feeding of dietary CD to pigs prevented extensive fatty hepatocytic infiltration and severe jaundice, but not hydropic degeneration induced by aflatoxin B1. Cadmium increased the toxicity of warfarin with severe lameness, subcutaneous hematomas in the ventral surface of the neck, and death.

Topics: Aflatoxin B1; Aflatoxins; Animal Feed; Animals; Cadmium; Carcinogens; Male; Metals; Swine; Swine Diseases; Warfarin

Pertinent literature on naturally occurring hemorrhagic diseases in poultry and livestock were reviewed and compared with reports on recent outbreaks of a hemorrhagic syndrome in swine. Epizootiologic, clinical, and hematologic data from porcine hemorrhagic disease suggest vitamin K-responsive hypoprothrombinemia. In weanling pigs, the toxicity of warfarin was compared with that in swine given tylosin and sulfamethazine antibacterial combination versus those given warfarin only. Toxicosis was induced in weanling swine fed warfarin daily at dose level of 0.055 mg/kg of body weight. Approximately 5 days after feeding was started, signs of poisoning appeared: lameness, anorexia, subcutaneous hematomata, melena, and periarticular enlargement. Administration of warfarin at dose level of 0.017 mg/kg did not cause clinical toxicosis, and 0.028 mg/kg produced significant increases in one-stage prothrombin time (OSPT) and activated partial thromboplastin time (APTT), but no evidence of clinical bleeding. When tylosin-sulfamethazine antibacterial combination was fed at normal and high dose levels concurrently with warfarin at dose level of 0.017 mg/kg of body weight, increase of clotting time, OPST, or APTT did not occur due to antibacterial influence. The antibacterial combination fed alone did not produce changes in clotting time, OSPT, APTT, fibrinogen, total protein, differential leukocyte count, or packed cell volume.

Topics: Animals; Anti-Bacterial Agents; Blood Coagulation; Hemorrhage; Hemostasis; Leucomycins; Prothrombin Time; Sulfamethazine; Swine; Swine Diseases; Warfarin

Topics: Animals; Arsenic Poisoning; Behavior, Animal; Cattle; Clinical Laboratory Techniques; Dogs; Education, Medical, Graduate; Education, Medical, Undergraduate; Environmental Health; Laboratories; Lead Poisoning; Mercury Poisoning; Nervous System; Plant Poisoning; Sheep; Sheep Diseases; Swine; Swine Diseases; Time Factors; Toxicology; Veterinary Medicine; Warfarin

Topics: Animals; Poisoning; Swine; Swine Diseases; Vitamin K; Warfarin